Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopamine D3 receptor (DRD3) was demonstrated to have important implications in schizophrenia, because it binds antipsychotic drugs and is abundant in the limbic system of the brain. Several groups attempted to find an association between a serine-to-glycine polymorphism at codon 9 of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. We conducted a case-control association study in Han Chinese schizophrenic patients from Taiwan, to examine the relationship of this serine-to-glycine polymorphism and schizophrenia. We noted no significant differences of genotype distribution, allele frequencies, or homozygosity proportion of this polymorphism between schizophrenic patients (N = 178) and controls (N = 100). When patients were divided according to sex, or presence or absence of family history, the differences were still not significant. Our study does not support the contention that the Ser9Gly polymorphism of the DRD3 gene plays a major role in schizophrenia.
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PMID:Further evidence of no association between Ser9Gly polymorphism of dopamine D3 receptor gene and schizophrenia. 903 4

As part of the European Multicentre Association Study of Schizophrenia (EMASS), we studied polymorphisms in the dopamine DRD2 and DRD3 receptor genes. The EMASS collaboration was established to create a large, statistically powerful sample of schizophrenic patients and controls from different European centres. Previous studies have suggested associations between schizophrenia and the Ser311Cys polymorphism in exon 7 of the dopamine DRD2 receptor gene [Arinami et al., (1994): Lancet 343:703-704] and a polymorphism Ser9gly in exon 1 of the dopamine DRD3 receptor gene [Crocq et al. (1992): J Med Genet 29:858-860]. We tested for these associations in samples of 373 and 413, and 311 and 306 patients and controls, respectively. We found no evidence for allelic association between schizophrenia and the Cys311 variant of the DRD2 receptor gene and no homozygotes for this variant were observed by any group. However, an excess of homozygotes for both alleles of the DRD3 polymorphism was observed in schizophrenic patients (chi2 = 8.54, P = 0.003, odds ratio = 1.64, 95% CI = 1.18-2.29). We also observed a significant excess of the 1-1 (Ser9Ser) genotype (chi2 = 8.13, P = 0.004, odds ratio = 1.7, 95% CI = 1.18-2.4). No evidence of heterogeneity between samples was detected and there was no evidence of an allelic association. These findings suggest that the rare Cys311 variant in exon 7 of the DRD2 receptor gene does not play a role in the pathogenesis of schizophrenia in European populations. Currently, our results do support the previous findings of an association between increased homozygosity of the Ser/Gly variant of the Dopamine D3 receptor gene and schizophrenia.
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PMID:European Multicentre Association Study of Schizophrenia: a study of the DRD2 Ser311Cys and DRD3 Ser9Gly polymorphisms. 951 83

Dopamine D3 receptor gene (DRD3) variants have been implicated in the pathogenesis of psychiatric disorders. Many studies, however, have failed to replicate the association of DRD3 with schizophrenia. A possible reason for this may lie in the definition of phenotype, which is traditionally based on psychiatric diagnosis. In this study we investigated the possibility that variants of the DRD3 gene might be associated with symptomatology in a sample of subjects affected by major psychoses. Two hundred and eleven inpatients affected by major psychoses were assessed by the Operational Criteria Checklist for Psychotic Illness (OPCRIT) and were also typed for the DRD3 variants using polymerase chain reaction techniques. Mania, depression, delusion, and disorganization were the four symptomatologic factors used as phenotype definitions. DRD3 variants were not associated with these symptomatologic factors, and consideration of possible stratification effects, such as sex and psychiatric diagnosis, did not reveal any association either.
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PMID:Dopamine D3 receptor gene not associated with symptomatology of major psychoses. 1049 Jul 2

Schizophrenia may be related to immunity as is suggested by many findings of altered immune parameters in schizophrenic patients. How immune alterations might be involved in the emergence of psychosis is still unclear. Clearly, however, the dopamine hypothesis has been confirmed in recent studies, which implies a crucial role for dopamine and the dopamine D2 receptor (D2R) within the pathogenesis of schizophrenia. The Dopamine D3 receptor (D3R) is considered to have autoreceptor properties modulating the synthesis and release of dopamine, thereby possibly antagonizing the dopamine D2-receptor-mediated effects of dopamine and has been found reduced in schizophrenic patients during acute psychosis and increasing in the advent of negative schizophrenic symptoms. Immune parameters apparently influence the expression of dopamine receptors by means of their capability to induce regulatory factors involved in the expression of dopamine receptor subtypes, such as the neurotrophins, associations of which with psychosis have been reported repeatedly. Here, we propose a hypothesis of immune alterations that influence the production of distinct neurotrophins such as BDNF and NGF that, as animal studies suggest, influence the expression of dopamine receptor subtypes. This mechanism could result in a decrease of D3R and a consecutive relative preponderance of D2R and thereby connect immune alterations and schizophrenia.
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PMID:Dopamine D3 receptor and schizophrenia: a widened scope for the immune hypothesis. 1654 Feb 54

Dopamine D3 receptor (DRD3) binds antipsychotic drugs and is abundant in the limbic system of the brain. It has been shown to play important roles in schizophrenia. A number of studies investigated the Ser9Gly polymorphism of the DRD3 gene to test its possible association with schizophrenia; however, the results were inconsistent. Our study aims to further evaluate the possible association between the Ser9Gly polymorphism and schizophrenia using a case-control association study within the Han Chinese population as well as a meta-analysis covering all previous studies. Our study, based on 329 schizophrenic patients and 288 controls, found no significant difference in the genotype or allele distributions of Ser9Gly polymorphism, the meta-analysis showed that the Ser9Gly polymorphism was not associated with Schizophrenia. Our study does not support the contention that the Ser9Gly polymorphism of the DRD3 gene plays a major role in schizophrenia in the Chinese population.
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PMID:The Ser9Gly polymorphism of the dopamine D3 receptor gene and risk of schizophrenia: an association study and a large meta-analysis. 1829 56

This review presents the findings of pharmacogenetic studies exploring the influence of gene variants on antipsychotic treatment response, in terms of both symptom improvement and adverse effects, in patients with schizophrenia. Despite numerous studies in the field, replicating findings across different cohorts that include subjects of different ethnic groups has been challenging. It is clear that non-genetic factors have an important contribution to antipsychotic treatment response. Differing clinical, demographic and environmental characteristics of the cohorts studied have added substantial complexity to the interpretation of the positive and negative findings of many studies. Pharmacogenomic genome-wide investigations are beginning to yield interesting data although they have failed to replicate the most robust findings of candidate gene studies, and are limited by the sample size, especially given the need for studying homogeneous cohorts. Most of the studies conducted on cohorts treated with single antipsychotics have investigated clozapine, olanzapine or risperidone response. These studies have provided some of the most replicated associations with treatment efficacy. Serotonergic system gene variants are significantly associated with the efficacy of clozapine and risperidone, but may have less influence on the efficacy of olanzapine. Dopamine D3 receptor polymorphisms have been more strongly associated with the efficacy of clozapine and olanzapine, and D2 genetic variants with the efficacy of risperidone. Serotonin influences the control of feeding behaviour and has been hypothesized to have a role in the development of antipsychotic-induced weight gain. Numerous studies have linked the serotonin receptor 2C (5-HT2C) -759-C/T polymorphism with weight gain. The leptin gene variant, -2548-G/A, has also been associated with weight gain in several studies. Pharmacogenetic studies support the role of cytochrome P450 enzymes and dopamine receptor variants in the development of antipsychotic-induced movement disorders, with a contribution of serotonergic receptors and other gene variants implicated in the mechanism of action of antipsychotics. Clozapine-induced agranulocytosis has been associated with polymorphisms in the major histocompatibility complex gene (HLA).
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PMID:Pharmacogenetics of response to antipsychotics in patients with schizophrenia. 2205 19